Current knowledge regarding the immunological responses in patients with pyelonephritis suggests the biochemical stability of bacterial antigens and cellular and humoral immune mechanisms may all be important contributing factors in the pathogenesis of this disease. Recent studies in our laboratory demonstrate that kidney tubule plasma membranes from pyelonephritic kidneys stimulate the blast transformation of autologous peripheral blood lymphocytes. Further studies to determine the importance of this observation demonstrate that bacterial antigenic components injected into rat and mouse kidneys cause pyelonephritic-like lesions; the severity of these lesions is genetically restricted and is dependent on host factors. Electron microscopy studies confirm the binding of peroxidase labeled LPS to the plasma membranes of cultured human and rat tubule cells. Kidney tubule cells from LPS responsive C3H/HeN mice bind more lipid A than the nonresponsive C3H/HeJ strain. The primary objective of this proposal will be to continue to investigate the potential immunological mechanisms which may be important in the pathogenesis of pyelonephritis in vivo. Rat and responder and nonresponder mouse kidneys will be infected with Proteus mirabilis and E. coli bacteria isolated from patients with chronic pyelonephritis. The persistence of the various specific bacterial antigens in rat, mice, and humans will be determined in vivo using flourescent antibody probes. Parallel experiments in vitro will evaluate the potential importance of the various cellular and humoral immunological mechanisms in the pathogenesis of this disease in animals and in man. Macrophages, polymorphonuclear leukocytes, T and B lymphocytes and antibodies may function separately or in concert to effect kidney tubule cell destruction during various phases of the infectious process. The direct effect of these immunological mediators on the kidney cells will be compared to their effect on kidney tubule cells sensitized with various purified bacterial antigens. This work will help to define the genetic factors, bacterial antigens and immunological mechanisms which may be important in the pathogenesis of pyelonephritis.